The HIV-1 envelope glycoproteins play a central role in virus entry into the host cell and in the induction of cytopathic effects. The envelope glycoproteins are also primary targets for the host cell immune response to HIV-1. Unfortunately, most of the humoral immune response to the envelope glycoproteins of HIV-1 appears to be directed at protein regions less important for function, suggesting that "antigenic masking" of functional regions occurs. One mechanism for this masking may be the heavy glycosylation state of the mature envelope glycoproteins, especially the gp120 exterior glycoproteins. The goal of this proposal is to study the role of glycosylation in modifying the immunogenicity of the HIV-1 envelope. We will attempt to construct, by site-directed mutagenesis, envelope glycoproteins that retain function but that exhibit decreases in glycosylation. These mutant envelope proteins will be used to elicit immune responses in mice. The humoral and cellular responses will be compared for various mutant and wild-type glycoproteins. The ability of the humoral responses to inhibit the function of mutant and wild-type HIV-1 envelope glycoproteins will be analyzed.